The human gammaherpesviruses Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus and murine gammaherpesvirus-68 (gHV68) are associated with B-cell lymphomas. The establishment of a chronic infection in B-cells is a critical step in the ability of these viruses to establish a life-long infection that may put infected cells at risk for transformation. gHV68 represents a small tractable animal model for gammaherpesvirus latency. These studies aim to utilize gHV68 as a model for understanding the role of NFkappaB in the establishment of chronic infection by gammaherpesviruses. NF-kB is necessary for the survival of B-cells infected with gHV68. In addition, NF-kappaB is required for achieving normal levels of chronic gHV68 infection in B-cells of mice. Here, two aspects of NF-kappaB signaling in B-cells upon infection with gHV-68 will be investigated: the specific NF-kappaB signaling pathways and subunits that are activated and the viral proteins that modulate these pathways. Characterization of these critical virus-cell interactions will provide a greater understanding of gammaherpesvirus-associated lymphoproliferative disorders and may thereby lead to novel therapeutic targets.